Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, in SCID mouse model for disseminated Mycobacterium avium complex infection.

In this study, profiles of infection due to Mycobacterium avium complex (MAC) in CB-17 SCID mice deficient in T and B cell functions were examined, when mice were given or not given a new benzoxazinorifamycin, KRM-1648 (KRM), during the course of infection. When mice were infected intravenously with MAC, the bacterial loads in their visceral organs were larger than those of their co-isogenic CB-17 counterparts. The incidence and the degree of gross lung lesions were less in SCID mice compared to CB-17 mice. Athymic BALB/c nude mice showed similar profiles of the infection. Beige mice showed more severe gross lesions and larger bacterial loads in the lungs than did SCID and athymic BALB/c nude mice. When MAC was infected subcutaneously into the hind footpads of mice, disseminated growth of organisms in the footpads, blood, and visceral organs was seen in SCID mice, but not in CB-17 or BALB/c mice. KRM exhibited the same level of therapeutic effect on SCID mice infected with MAC via the intravenous route in terms of inhibiting bacterial growth in the lungs and kidneys, as in cases of CB-17 and BALB/c mice with normal T-cell functions. In beige mice, the degree of growth inhibition of MAC due to KRM treatment was significantly greater than that achieved in SCID mice.